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Subspecialties Retina, Imaging & Diagnostics

The H Factor

Researchers have found increased levels of complement factor H-related Protein 4 (FHR-4) in plasma and serum samples of 484 late AMD patients (characterized by geographic atrophy and/or choroidal neovascularization) compared with 522 phenotype controls (1). Further, the research team – based out of Cardiff University, Queen Mary University of London, the University of Manchester, and Radboud University Medical Center – found FHR-4 present in the AMD-affected parts of the eye.

To discover whether increased levels of FHR-4 were a cause or consequence of AMD, the team turned to genetics. The genes coding for factor H, FHR-4 and other FH-family proteins are typically found in a tight cluster on chromosome 1. A genome-wide association study revealed that variants in this gene cluster have the biggest effect on FHR-4 levels, overlapping with other chromosome 1 variants that determine a well-established 20-year-old genetic risk of AMD. The team’s findings suggest that genetically determined increases in blood FHR-4 levels lead to more FHR-4 in the eye, which in turn increase the risk of the uncontrolled complement activation that drives the disease. The team hopes its findings will provide a new route to treatment by restoring complement control in the eye.


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  1. V Cipriani et al., Nature, 11, 778 (2020). PMID: 32034129.

About the Author

Phoebe Harkin

Associate Editor of The Ophthalmologist

I’ve always loved telling stories. So much so, I decided to make a job of it. I finished a Masters in Magazine Journalism and spent three years working as a creative copywriter before itchy feet sent me (back)packing. It took seven months and 13 countries, but I’m now happily settled on The Ophthalmologist, where I’m busy getting stuck into all things eyeballs.

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